Abstract
Genome‐, transcriptome‐ and proteome‐wide measurements provide insights into how biological systems are regulated. However, fundamental aspects relating to which human proteins exist, where they are expressed and in which quantities are not fully understood. Therefore, we generated a quantitative proteome and transcriptome abundance atlas of 29 paired healthy human tissues from the Human Protein Atlas project representing human genes by 18,072 transcripts and 13,640 proteins including 37 without prior protein‐level evidence. The analysis revealed that hundreds of proteins, particularly in testis, could not be detected even for highly expressed mRNAs, that few proteins show tissue‐specific expression, that strong differences between mRNA and protein quantities within and across tissues exist and that protein expression is often more stable across tissues than that of transcripts. Only 238 of 9,848 amino acid variants found by exome sequencing could be confidently detected at the protein level showing that proteogenomics remains challenging, needs better computational methods and requires rigorous validation. Many uses of this resource can be envisaged including the study of gene/protein expression regulation and biomarker specificity evaluation.
Highlights
Delineating the factors that govern protein expression and activity in cells is among the most fundamental research topics in biology
Tissues were collected by the Human Protein Atlas (HPA) project (Fagerberg et al, 2014), and adjacent cryosections were used for paired transcriptome and proteome analysis
Proteomic profiling by mass spectrometry resulted in the identification and intensity-based absolute quantification of a total of 15,210 protein groups with an average of 11,005 (Æ 680 SD) protein groups per tissue at a false discovery rate (FDR) of < 1% at the protein, peptide and peptide-spectrum match (PSM) level (Fig EV1A)
Summary
Delineating the factors that govern protein expression and activity in cells is among the most fundamental research topics in biology. While it is generally accepted that the quantities of proteins vary greatly within and across different cell types, tissues and body fluids (Kim et al, 2014; Wilhelm et al, 2014), this has not been analysed systematically for many human tissues. It is not very clear yet how the many anabolic and catabolic processes are coordinated to give rise to the often vast differences in the levels of proteins.
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